| With the change of environment and lifestyle,diabetes and malignant tumors have become important causes of death in our country and even around the world.Epidemiological data show that the risk of diabetes accompanied with malignancy is significantly increased.For patients with diabetes and malignant tumors,hypoglycemic drugs need be used long-term or even life long,so whether hypoglycemic agents can affect the development and prognosis of tumors has attracted much attention.The antidiabetic drugs commonly used in type 2 diabetes include insulin,metformin,GLP-1 R(glucagon like peptide-1 Receptor,GLP-1R)agonists.Some studies have shown that insulin may promote the development and progression of malignant tumor cells.Metformin can inhibit the development of esophageal cancer,gastric cancer,pancreatic cancer and other malignant tumors.GLP-1R agonist is a new type of hypoglycemic agent,It has good hypoglycemic effect and is convenient to use,therefore,it has been favored by more and more diabetic patients.After binding with GLP-1R,GLP-1 can affect cell proliferation and apoptosis by signaling pathways,such as PI(3)K and Wnt,so it may affect the occurrence and development of malignant tumor cells.At present,the clinical research on GLP-1 receptor agonists is mainly focused on the relationship between the short-term GLP-1R agonist exenatide and tumor,current clinical studies have found that exenatide has an certain inhibitory effect on cell proliferation,migration and other biological behavior of malignant tumor cells.But the study on the long-acting GLP-1R agonist liraglutide is not enough,In addition,the clinical studies previous on the GLP-1 receptor agonists are mainly focus on the short-termGLP-1R agonist exenatide and pancreatic cancer,breast cancer,prostate cancer,and the clinical research on the tumor of colon cancer,gastric cancer,lung cancer is still not too much.so this study intend to research the effect of the long-term GLP-1 receptor agonist on human colon cancer,gastric cancer,lung cancer cell lines,to observe its effects on the biological behaviors of the tumor cell proliferation,migration,apoptosis,it will provide experimental evidence whether the type 2 diabetes mellitus accompanied with colon cancer,gastric cancer or lung cancer can use the the long-term GLP-1 receptor agonist liraglutide safely.Objective:To investigate the effect of new hypoglycemic drugs GLP-1 receptor agonist liraglutide on the biological behaviors of human colon cancer cell line HCT116,SW480,human gastric cancer cell line SGC7901,BGC823,human lung cancer cell line H1299,in order to provide experimental reference whether the patients of type 2 diabetes accompanied with colon cancer,gastric cancer or lung cancer can using the GLP-1 receptor agonists liraglutide safely.Method:1.To study the effect of Liraglutide on the HCT116,SW480 human colon cancer cell line,BGC823,SGC7901 human gastric cancer cell line and H1299 human lung cancer cell line,the effects of liraglutide on proliferation of tumor cells were detected by CCK-8 method;the effects of liraglutide on Colony formation of the tumor cell communities were detected by clone formation assay;the effect of liraglutide on the migration of tumor cells were detected by scratch method;the effect of liraglutide on apoptosis of tumor cell were detected byflow cytometric.2.Q-PCR techniques were used to detect the expression of GLP-1R mRNA in HCT116,SW480 human colon cancer cell line,BGC823,SGC7901 human gastric cancer cell line and H1299 human lung cancer cell line.Results:1.We take the GLP-1 receptor agonist liraglutide to affect the human colon cancer cell line HCT116 and SW480,24? 48 ?72?96hours later,In the group of cell line HCT116 and SW480,compared with the control group,the tumor cell proliferation rates of 10nmol/L,100nmol/L,1000nmol/L group have no significant change(P > 0.05).After liraglutide have affected the human colon cancer cell line HCT116 and SW480 48 h later,Compared with the control group,there was no significant difference in the number and size of clone formation(P > 0.05);In the group of cell line HCT116,tumor cell migration distance of the control group,10nmol/L,100nmol/L,1000nmol/L drug group was respectively 37.70 + 1.70 ?m,34.64+ 2.17 ?m,37.82 + 1.78 ?m,36.61 + 2.14 ?m,In the group of cell line SW480,tumor cell migration distance of the control group,10nmol/L,100nmol/L,1000nmol/L drug group was respectively 26.47±2.24 ?m,26.90±1.88 ?m,23.21±0.61 ?m,25.08±2.17 ?m(compared with the control group,P > 0.05);In the group of cell line HCT116,the tumor cells apoptosis of the control group,10nmol/L,100 nmol,1000nmol/L liraglutide drug group was respectively 3.03%,2.83%,3.57%,3.60%,In the group of cell line SW480,the tumor cells apoptosis of the control group,10nmol/L,100nmol/L,1000nmol/L drug grougroup was respectively 3.00%,2.40%,4.23%,4.17%(compared with the control,P > 0.05).2.We take the GLP-1 receptor agonist liraglutide to affect the human gastric cancer cell line BGC823 and SGC7901,24? 48 ?72?96hours later,In the group of cell line BGC823 and SGC7901,compared with the control group,the tumor cell proliferation rates of 10nmol/L,100nmol/L,1000nmol/L group have no significant change(P > 0.05).After liraglutide have affected the human gastric cancer cell line BGC823 and SGC7901 48 h later,compared with the control group,the tumor cell colony formation rate of the 1000nmol/L group in the cell line BGC823 and SGC7901was97.33 % and 103.01%(P > 0.05),Compared with the control group,there was no significant difference in the number and size of clone formation;in the group of cell line BGC823,tumor cell migration distance of the control group,10nmol/L,100nmol/L,1000nmol/L drug group was respectively 23.73±1.47 ?m,21.24±0.80 ?m,22.27±1.27 ?m,20.52±0.55 ?m,in the group of cell line SGC7901,tumor cell migration distance of the control group,10nmol/L,100nmol/L,1000nmol/L drug group was respectively31.08±1.95 ?m,31.27±1.75 ?m,30.52± 2.48 ?m,28.14±1.13 ?m(compared with the control group,P > 0.05);in the cell line BGC823,the tumor cells apoptosis of the control group,10nmol/L,100nmol/L,1000nmol/L drug group was respectively 2.20,2.03%,2.30%,2.07%;in the cell line SGC7901,the tumor cells apoptosis of the control group,10nmol/L,100nmol/L,1000nmol/L drug group was respectively 5.63%,5.73%,5.87%,5.50%(compared with the control group,P > 0.05).3.We take the GLP-1 receptor agonist liraglutide to affect the liraglutide to affect the human colon cancer cell line HCT116 and SW480,24? 48 ?72?96hours later,In the group of cell line H1299,compared with the control group,the tumor cell proliferation rates of 10nmol/L,100nmol/L,1000nmol/L group have no significant change(P > 0.05).After liraglutide have affected the human lung cancer cell line1299 48 h later,Compared with the control group,there was no significant difference in the number and size of clone formation(P > 0.05);tumor cell migration distance of the control group,10nmol/L,100nmol/L,1000nmol/L drug group was respectively 23.27±1.51?m,25.07±1.91?m,23.74±1.47?m,25.48±2.91?m um(compared with the control group,P > 0.05);the tumor cells apoptosis of the control group,10nmol/L,100nmol/L,1000nmol/L liraglutide drug group was respectively2.00%,2.37%,2.17%,1.90%(compared with the control group,P > 0.05).4.The results of Q-PCR showed that the expression of GLP-1R mRNA was negative on the HCT116,SW480 human colon cancer cell line,BGC823,SGC7901 human gastric cancer cell line,H1299 human lung cancer cell line.Conclusion:the expression of GLP-1R mRNA were not detected in the human colon cancer cell line HCT116,SW480 and the human gastric cancer cell line BGC823,SGC7901,the human lung cancer cell line H1299,GLP-1R agonist liraglutide has no effect on the proliferation,migration,apoptosis of the human colon cancer cell line,the human gastric cancer cell line andthe human lung cancer cell line. |
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